title: Resistin derived from diabetic perivascular adipose tissue up-regulates vascular expression of osteopontin via the AP-1 signalling pathway.
abstract: Perivascular adipose tissue (PVAT) is implicated in the development of vascular diseases; however, the roles of PVAT on OPN expression in diabetic vasculature remain to be determined. This study investigated the role of adipokines derived from diabetic PVAT in regulating the vascular expression of OPN and explored the mechanisms involved. Aortic sections of ob/ob and high-fat diet (HFD)-induced obese (DIO) mice showed an increased expression of OPN, which was paralleled by increased amounts of PVAT characterized by enlargement of adipocytes. In the earlier phase of HFD feeding, macrophage infiltration was mainly localized to the area of PVAT at which adipocytes were enlarged, suggesting a potential link of activated adipocytes to macrophage infiltration. PVAT sections of ob/ob and DIO mice revealed a significantly greater number of macrophages with increased expression of adipokines, including resistin and visfatin. The distribution of resistin in PVAT mostly co-localized with macrophages, while visfatin was expressed in macrophages and other cells. In in vitro studies, OPN expression in vascular smooth muscle cells (VSMCs) co-cultured with PVAT of DIO mice was significantly increased, which was attenuated by a resistin-neutralizing antibody. Likewise, resistin up-regulated expression of OPN mRNA and protein in cultured VSMCs and the pivotal role of AP-1 in resistin-induced OPN transcription was demonstrated. Resistin produced by PVAT plays a pivotal role in the up-regulated expression of OPN in the diabetic vasculature via a signalling pathway that involves activation of AP-1.
authors.affiliation: Medical Research Centre for Ischaemic Tissue Regeneration, Pusan National University, Yangsan, Gyeongnam, Republic of Korea.
authors.forename: So Youn
authors.initials: SY
authors.lastname: Park
authors.forename: Kyu Hee
authors.initials: KH
authors.lastname: Kim
authors.forename: Kyo Won
authors.initials: KW
authors.lastname: Seo
authors.forename: Jin Ung
authors.initials: JU
authors.lastname: Bae
authors.forename: Yun Hak
authors.initials: YH
authors.lastname: Kim
authors.forename: Seung Jin
authors.initials: SJ
authors.lastname: Lee
authors.forename: Won Suk
authors.initials: WS
authors.lastname: Lee
authors.forename: Chi Dae
authors.initials: CD
authors.lastname: Kim
mesh_terms: D000273:Adipose Tissue / Q000378:metabolism*; D000818:Animals; D001011:Aorta; D001483:Base Sequence; D001835:Body Weight; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000235:genetics / Q000378:metabolism*; D059305:Diet, High-Fat / Q000009:adverse effects; D004195:Disease Models, Animal; D005786:Gene Expression Regulation; D008264:Macrophages / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008820:Mice, Obese; D008969:Molecular Sequence Data; D032389:Myocytes, Smooth Muscle / Q000378:metabolism; D054409:Nicotinamide Phosphoribosyltransferase / Q000235:genetics / Q000378:metabolism; D009765:Obesity; D053495:Osteopontin / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D052243:Resistin / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D018808:Transcription Factor AP-1 / Q000235:genetics / Q000378:metabolism*; D015854:Up-Regulation
chemical_list: D016207:Cytokines; D052243:Resistin; C499623:Retn protein, mouse; C506896:Spp1 protein, mouse; D018808:Transcription Factor AP-1; D053495:Osteopontin; D054409:Nicotinamide Phosphoribosyltransferase; C495867:nicotinamide phosphoribosyltransferase, mouse
keywords: OPN; PVAT; macrophage; obesity; resistin